Polybrominated diphenyl ethers (PBDEs) are commonly used as fire retardants in consumer products such as electronics and furniture containing polyurethane foam. Structurally similar to polychlorinated biphenyls (PCBs), several PBDE congeners perturb hormonal signaling and are toxic to the nervous and reproductive systems of developing animals. Human body burdens have increased over the last several decades and are highest in the United States (US), where levels are more than an order of magnitude higher than in Asian and European populations in which PBDE levels are associated with decreased birth outcomes and increased risk of cryptorchidism. Diet and the indoor environment (dust, air) are likely important factors that contribute to personal exposure, but the predominant route of exposure is not known. Indeed, in a 2006 report on PBDEs, the US Environmental Protection Agency identified the "need for improved understanding of exposure to these chemicals and the associated hazards." We propose a comprehensive approach to examining human exposure to PBDEs. The proposed study has been designed to address a range of important gaps that exist in the PBDE research base and would represent the most complete assessment of human PBDE exposure to date. In a cohort of fifty Massachusetts residents, we will conduct three rounds of exposure sampling (at six month intervals) and examine three microenvironments: the home, workplace, and car. During each sampling round, we will concurrently assess PBDEs at multiple steps of the exposure-response continuum by (a) estimating the PBDE content of consumer products (potential sources) using a portable x-ray fluorescence analyzer, (b) measuring PBDEs in dust collected from the home, workplace and car (key microenvironments), (c) measuring PBDEs in personal air and hand-wipe samples (personal exposure), (d) measuring PBDEs in human serum (total absorbed dose), and (e) measuring hormone levels (potential early effects). This powerful study design will generate a rich dataset of repeated exposure measures and allow for a longitudinal assessment of PBDE body burden and hormone levels. Accordingly, the proposed research will provide a more complete understanding of how PBDEs enter the indoor environment, how the general population is exposed to PBDEs, which exposure routes contribute most to total absorbed dose, and the extent to which PBDE exposure may be associated with changes in hormone levels in humans. PUBLIC HEALTH RELEVANCE: The levels of polybrominated diphenyl ethers (PBDEs) found in the bodies of Americans have increased for decades and are an order of magnitude higher than in other countries where a few studies have found associations with adverse health outcomes. Although the indoor environment is hypothesized to be the major source of these flame retardants, the sources and routes of human exposure are not well understood. The proposed project will provide a more complete understanding of how PBDEs enter the indoor environment, how people are exposed, and the extent to which they may be associated with human hormones levels.